This proposal deals with the metabolic basis of recurrent calcium urolithiasis in man. There are two major subdivisions in the work: basic mechanisms of transport processes in the renal tubule, and clinical studies of the mechanisms of hypercalciuria and recurrent renal calculi. The basic studies are concerned with studying calcium transport processes and their control in the renal tubule as studied by micropuncture methods; and with uric acid transport in isolated vesicles from the brush border membrane. The clinical studies are concerned with an evaluation of a group of patients with recurrent calcium orolithiasis in terms of calcium metabolism, parathyroid function, vitamin D status, oxalate metabolism, uric acid metabolism, renal tubular function, and bone turnover in an effort to develop means of classifying the different forms of so-called idiopathic hypercalcuria, and thereby develop more rational means of treatment. Specifically, we are evaluating an oral calcium tolerance with measures the changes in serum and urinary calcium, plasma parathyroid hormone, and nephrogenous cyclic AMP as a means of distinguishing the various types of hypercalciuria. In addition, we are using this test to evaluate calcium metabolism in patients with primary hyperparathyroidism before and after surgery so as to determine the persistence of abnormalities in calcium metabolism and/or parathyroid function post-operatively.